Abnormal glucose tolerance generally designates a state where the fasting blood glucose level is in a range of 110 mg/dl to less than 126 mg/dl, or a state where the 2-hour value in an oral glucose tolerance test is 140 mg/di to 199 mg/dl, and is also called borderline diabetes. Although the patients of borderline diabetes have abnormal blood glucose levels, they are not exactly considered to have diabetes; however, if the patients leave the condition untreated, they are highly likely to become diabetic. The condition is thus called prediabetes. Further, arteriosclerosis is known to advance at this stage. Therefore, in terms of preventive medicine as well, it is important to detect patients in a prediabetic stage.
In the diagnosis of diabetes, primary screening is generally conducted first with a urine glucose test or a fasting blood glucose level test, and, if such tests are positive, a glucose tolerance test is performed to make a definite diagnosis. In recent years, HbA1C or fructosamine in the blood may also be tested before a glucose tolerance test using glucose.
However, side effects caused by administration of a large amount of glucose have been indicated with regard to the glucose tolerance test using glucose. Further, the test requires test subjects to be restrained for several hours, and for blood to be repeatedly collected. Because this therefore imposes a great physical burden on test subjects, the test can only actually be carried out on a limited number of test subjects. Further, the results of HbA1C or fructosamine cannot be known until the next hospital visit, thus posing the drawback of insufficient rapidity. The tests performed before these tests, such as the urine glucose test or fasting blood glucose level test, have problematic low sensitivity since they often show negative results of urine glucose or normal results of blood glucose levels even though the test subjects are diabetic; thereby, they miss many cases of diabetic patients. Accordingly, these known methods for diagnosing diabetes are incapable of determining a prediabetic stage in which diabetes has not yet been developed, such as borderline diabetes, or a condition even before borderline diabetes (a condition having insulin resistance or hyperinsulinemia without insulin resistance).
In recent years, as a diabetes diagnosis method, a method of intravenously administering acetic acid, oleic acid, or palmitic acid labeled with 13C, and measuring the increasing rate of 13C concentration in the CO2 in the expired air with a breath test, thereby diagnosing insulin hyposecretion-type diabetes has been suggested (Patent Document 1). However, it is unknown whether this method is capable of diagnosing a condition even before borderline diabetes (a condition having insulin resistance or hyperinsulinemia without insulin resistance).
Examples of underlying diseases showing insulin resistance include liver diseases. In particular, liver cirrhosis patients have a nutritionally typical pathological condition of protein-energy malnutrition (PEM). Moreover, a significant percentage of the liver cirrhosis patients also have comorbid insulin resistance. Thus, a correlation between comorbid insulin resistance and liver cancer has also been reported. However, a method for diagnosing comorbid insulin resistance in liver cirrhosis patients has not been established. For the diagnosis of PEM degree, indirect calorimetry for detecting saccharideilipid combustion ratio has been used. The saccharide/lipid combustion ratio can be calculated as a respiratory quotient. It has been reported that the prognosis of liver cirrhosis or liver cancer worsens when the respiratory quotient is decreased to 0.85 or less by a decrease in saccharide combustion and/or an increase in fat combustion. Further, it has also been reported that the respiratory quotient significantly decreases with the increase in severity of liver cirrhosis (Non-patent Document 1). More specifically, by measuring the saccharide/lipid combustion ratio, it is possible to determine the prognosis or severity of liver cirrhosis, liver cancer, etc. However, known methods using calculation of respiratory quotient have little practicability, and it is considered impossible to easily grasp the nutritional status objectively.
Meanwhile, applying so-called a labeled C-breath test, which is a method of measuring 13CO2 excreted in expired air as carbon dioxide after administration of 13C-labeled glucose, to the diagnosis of diabetes has been proposed (Patent Documents 2 to 4). More specifically, Patent Document 2 discloses a method for diagnosing the presence or absence of diabetes as well as the type of diabetes (type I diabetes or type II diabetes) by performing a breath test using glucose wherein the carbon at a specific position is replaced by 13C, and determining the degree of increase in 13CO2 concentration excreted in expired air. Further, Patent Documents 3 and 4 disclose performing a breath test using 13C-labeled glucose as in Patent Document 2 and diagnosing a diabetic patient or an insulin-resistant patient based on an index such that the ratio of 13C to 12C (13C/12C) in expired air that is lower than the ratio of a healthy subject, the ratio being calculated from the concentration of 13CO2 excreted in the expired air.
However, these documents nowhere disclose or suggest combining a labeled C-breath test using glucose with a labeled C-breath test using fatty acid, thereby enabling highly accurate detection of a saccharide/lipid combustion ratio that can replace respiratory quotient.